The museum was founded by the Chilean architect and antiquities collector Sergio Larraín García-Moreno, who had sought premises for the display and preservation of his private collection of pre-Columbian artefacts acquired over the course of nearly fifty years.

With the support of Santiago's municipal government at the time, García-Moreno secured the building and established the museum's curatorial institution.

In January 2014, as a result of a partnership with Minera Escondida and BHP Billiton, the museum inaugurated a new phase designed by Chilean architect Smiljan Radic which involved a 70% expansion of the area, increasing exhibition spaces, storage, and the conservation laboratory.

[3] Items in the museum's collections are drawn from the major pre-Columbian culture areas of Mesoamerica, Intermediate / Isthmo-Colombian, Pan-Caribbean, Amazonia and the Andean.

The original collection was acquired based on the aesthetic quality of the objects, instead of their scientific or historical context.